1. Field of the Invention
The invention relates to the methods and apparatus for equilibrating an aqueous solution such as buffer liquid or blood with gas. Particularly the invention is concerned with an apparatus and process for equilibrating solutions for preparation of standards useful in quality control of laboratory instrumentation. For example, quality control for blood gas analyses in the clinical laboratory comprises both calibration of the blood gas analyzer as well as reference controls for the analyzer. The invention provides these controls for one- and two-point calibrations and also provides tonometered samples for reference control. In addition, the invention can be used for blood P.sub.50 oxyhemoglobin-dissociation curve determination and for other laboratory instrumentation calibration. A simple, fast and error-free tonometry system has great practical application in the clinical and research laboratory.
2. Prior Art
There is an increasing widespread use of blood gas analyzers in clinical laboratories. The electrode sensors which measure PO.sub.2, PCO.sub.2 and pH in these analyzers have inherent problems maintaining accuracy and reliability. This has accelerated the need for methods to assure quality control of these devices. Tonometry (the equilibration of gas partial pressures between liquid and gas) is considered to be the preferred method in providing the standards to be used for both calibration and reference controls. Simple as the problem of tonometering an aqueous solution (e.g. blood) with a known gas mixture may appear at first, it is often difficult to accomplish because of several conditions which have to be met. The ideal tonometer should have the following characteristics: (1) it should equilibrate the partial pressures of gases in an adequate quantity of sample with a minimal volume of known gas composition while maintaining the pressure at the gas-liquid interface at a known level; (2) the equilibration should occur at a known and controlled temperature, at a rapid rate, and without dehydration (or hemolysis to blood); (3) transfer of the sample to the analyzing chamber must be such as to avoid any deteriorating air contamination and such transport should be accomplished rapidly and easily; and (4) the tonometer should be simple to use, easy to clean and maintain, compact, and cost effective. The conditions of adequate gas-liquid equilibration, temperature control, and gas humidification have been achieved by many of the present instruments. However, the problem of transport of the tonometered sample to the analyzer has not been solved.
There are four general tonometer concepts which have been developed. Perhaps the most widely used method to date is the thin film approach. The instrument used with this method operates by introducing a known gas composition over the surface of the liquid in a swirling or rotating flask so that a large surface area of the liquid is placed in contact with the gas. This method generally requires twenty to thirty minutes and present instruments prepare only one sample at a time. This concept is not entirely satisfactory since the sample may be altered as it is transferred to a transport vessel.
A second method gaining much popularity today allows analyzed gas to bubble through the liquid sample to achieve a gas-liquid equilibration. The tonometer used with this process is inherently the simplest and cheapest type available. Instruments used with this approach employ multiple chambers for up to three separate simultaneous sample preparations. With this bubble method it is assumed that the gas-liquid interface pressure is at ambient level and this assumption may not be correct. A pressure difference is caused by (1) the increased hydrostatic pressure inside the bubble which is located below the liquid sample surface, and (2) the increased pressure inside the bubble due to surface tension when the bubble diameters are very small.
The problem of sample transportation has not been effectively solved since current bubble tonometers require an intermediate transport vessel for delivery of the sample to the analyzer. Air contamination is a possibility whenever the sample is transferred to an intermediate chamber between the location of tonometry and the location where the sample is analyzed.
Another tonometer design which is losing popularity uses oscillation or vibration of the sample within a temperature-controlled bath while a gas stream of known concentration passes over the surface. A fourth design makes use of highly gas permeable, liquid impermeable membranes or tubes to equilibrate a gas placed on one side of the membrane with the liquid on the other. Presently, there are no practical membrane tonometers available. The last two described designs have the same transport problems as the others previously described.